ArticleThe Journal of pharmacology and experimental therapeutics2016
Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons.
Article in The Journal of pharmacology and experimental therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Article
- Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate.Journal of neuroinflammation · 2024Article
- A longitudinal MRI and TSPO PET-based investigation of brain region-specific neuroprotection by diazepam versus midazolam following organophosphate-induced seizures.Neuropharmacology · 2024Article
- Cardiovascular responses of adult male Sprague-Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone.Archives of toxicology · 2024Article
- Article
- Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.Frontiers in toxicology · 2024Article
- Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus.Neurobiology of disease · 2023Article
- Adverse effect propensity: A new feature of Gulf War illness predicted by environmental exposures.iScience · 2023Article
- Chemical exposures and suspected impact on Gulf War Veterans.Military Medical Research · 2023Article
- Peripheral and central effects of NADPH oxidase inhibitor, mitoapocynin, in a rat model of diisopropylfluorophosphate (DFP) toxicity.Frontiers in cellular neuroscience · 2023Article
- Succinate prodrugs in combination with atropine and pralidoxime protect cerebral mitochondrial function in a rodent model of acute organophosphate poisoning.Scientific reports · 2022Article
- Veteran-derived cerebral organoids display multifaceted pathological defects in studies on Gulf War Illness.Frontiers in cellular neuroscience · 2022Article
- Persistent neuropathology and behavioral deficits in a mouse model of status epilepticus induced by acute intoxication with diisopropylfluorophosphate.Neurotoxicology · 2021Article
- Neurodegenerative Implications of Neuronal Cytoplasmic Protein Dysfunction in Response to Environmental Contaminants.Neurotoxicity research · 2021Review
- Acid is a potential interferent in fluorescent sensing of chemical warfare agent vapors.Communications chemistry · 2021Article
- The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons.Neuroscience insights · 2021Article
- Sex-specific acute and chronic neurotoxicity of acute diisopropylfluorophosphate (DFP)-intoxication in juvenile Sprague-Dawley rats.Current research in toxicology · 2021Article
- Acute administration of diazepam or midazolam minimally alters long-term neuropathological effects in the rat brain following acute intoxication with diisopropylfluorophosphate.European journal of pharmacology · 2020Article
- Allopregnanolone and perampanel as adjuncts to midazolam for treating diisopropylfluorophosphate-induced status epilepticus in rats.Annals of the New York Academy of Sciences · 2020Article
- The chemical convulsant diisopropylfluorophosphate (DFP) causes persistent neuropathology in adult male rats independent of seizure activity.Archives of toxicology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs.
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